The objectives are to clarify selected issues related to the causation and classification of affective disorders (manic-depressive illnesses). The primary focus is on the genetic basis for bipolar and unipolar forms of depressive illness. The research setting is the Old Order Amish community of Lancaster County, Pennsylvania. This is a homogeneous, endogamous (in-bred) group, where total genealogical assessment is possible, making it uniquely suited for identification and control of genetic, as well as social-environmental, variables. There will be a full ascertainment (period prevalence) of cases of mental disturbance for a three year period. A Board of five psychiatrists will provide independent diagnoses of the clinical case materials. Confirmed instances of primary affective disorders will serve as probands for extensive pedigree analysis in the extended families. Pedigrees will be selected with multiple cases of manic-depressive illness and controls will be well siblings in those families, in addition to pedigrees free from mental illness. Evidence will be sought to confirm genetic, biochemical, and behavioral factors in the etiology of the illness and the actual mode of inheritance involved. Methods will include: familial aggregation study, computationand comparison of morbid risk (within affected pedigrees and between sick and well family lines), and the possible linkage of bipolar-unipolar disorders to a medical marker by analysis of blood types, color blindness and other known genetic conditions.